Abstract
Midbrain dopaminergic neurons are responsible for several functions in the reward system, control of emotion, motivation, cognition, and motor behavior. A set of well-characterized transcription factors involved in specification, neurogenesis, and neuronal differentiation determines the fate of these neurons and modulates their survival and maintenance postnatally. Identifying novel molecular connections with these factors might, therefore, lead to a better understanding of physiology as well as dysfunction and degeneration of these neurons in Parkinson's disease. To explore the links between developmental pathways and to identify novel linkages, we examined the correlations of phylogenetic profiles of these factors with those of the entire human proteome. Our analysis revealed two distinct evolutionary pathways comprising the early and late developmental factors and new linkages with these developmental cascades. These results suggest an evolutionary scenario for the development of the midbrain and dopaminergic neurons, with potential novel links to the canonical and non-canonical functions of the transcription factors.
Highlights
Mesencephalic dopaminergic neurons are the primary source of dopamine in the central nervous system
The transcription factors involved in the early and late development of midbrain dopaminergic neurons may have evolved in a concerted manner as part of a single overall developmental pathway
We considered the degree of correlation among the phylogenetic profiles of meDA neuron developmental transcription factors
Summary
Mesencephalic dopaminergic (mesDA) neurons are the primary source of dopamine in the central nervous system. Dopaminergic neurons in the SNpc innervate dorsal striatum forming the nigrostriatal pathway and the VTA neurons give rise to the mesolimbic and mesocortical (mesocorticolimbic) systems by innervating the nucleus accumbens and olfactory tubercle, respectively [1,2,3,4,5,6] These pathways perform several functions in the reward system, control of emotion, motivation, cognition, and motor behavior. The development of dopaminergic neurons in the ventral midbrain involves a cascade of early and late developmental events, including regional specification, induction, differentiation, postmitotic development, mitigation, and axonal outgrowth These events are controlled by a set of well-characterized transcription factors [2,9]
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